This proposal is in response to research topics number 8-DNA polymorphisms and number 2-Racial and ethnic differences of PAR-98-021; the PI is an established investigator. Hypertension (HTN) is the most common chronic disease in the U.S. and is believed to have both genetic and environmental etiologies. Its prevalence increases with age, and there are marked racial differences in its prevalence, severity and sequelae. The beta2-adrenergic receptor (beta2AR) gene has two common coding region polymorphisms, at codons 16 (Arg or Gly) and 27 (Gln or Glu), and the Gly16 and G1n27 forms exhibit enhanced receptor down- regulation. We hypothesize that the Gly16 and/or Gln27 homozygous genotypes or alleles of the beta2AR are associated with HTN, racial differences in HTN, and/or a minimal nighttime blood pressure (BP) decline. We make these hypotheses because beta2ARs contribute to BP regulation through several mechanisms, and beta2AR down-regulation could contribute to development of HTN. beta2AR genotypes may also be associated with racial differences in HTN since studies have shown blacks are less responsive to beta2AR stimulation than whites, a finding consistent with racial differences in beta2AR genotypes. Finally, 25-40 percent of hypertensives do not exhibit the normal nighttime BP decline, which may lead to an increased risk of target organ damage and death. Because studies in asthmatics have shown the Gly16 allele is associated with nighttime worsening of asthma, we hypothesize the beta2AR polymorphisms may also be associated with minimal nighttime BP decline. The specific aims are to: 1a) determine if the beta2AR polymorphisms are associated with HTN by comparing beta2AR genotypes and allele frequencies at codons 16 and 27 between 160 hypertensives and 160 normotensives (equal numbers of blacks and whites); 1b) determine if the beta2AR gene is associated with racial differences in HTN by evaluating the association between the beta2AR gene and HTN independently by race (in blacks and white) and by comparing beta2AR genotypes and allele frequencies between hypertensive blacks and whites; 2) assess the relationship between beta2AR gene and nighttime BP decline by comparing codon 16 and 27 genotypes and alleles between at least 25 nocturnal BP "dippers" and 25 "nondippers" as determined by 24 h ambulatory BP monitoring. These pilot studies are important because they will provide important preliminary evidence about the beta2AR as a HTN gene, and whether this gene is associated with racial differences in HTN. Positive findings would stimulate significant further research, and if the beta2AR proved to be a HTN gene, especially one involved in racial differences in the disease, then strategies aimed at disease prevention, targeted antihypertensive therapy or gene therapy might be developed. Documentation of such an association between beta2AR genotypes/alleles and nighttime BP decline would be especially significant since the nocturnal BP decline appears to be a major determinant of target organ damage and may be an important cause of racial differences in HTN sequelae. Better understanding of the mechanisms controlling nighttime BP could lead to improved treatment strategies and decreased target organ damage from HTN.